Sorafenib for Treatment of Hepatocellular Carcinoma

Leathers, James; Balderramo, Domingo; Prieto, John; Diehl, Fernando; Gonzalez-Ballerga, Esteban; Ferreiro, Melina; Carrera, Enrique; Barreyro, Fernando J.; Díaz-Ferrer, Javier; Singh, Dupinder; Mattos, Ângelo Zambam de; Carrilho, Flair José; Debes, José D.

doi:10.1097/mcg.0000000000001085

Cited by 21 publications

(7 citation statements)

References 34 publications

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“…The median OS was 10.5 months overall, a similar figure to the SHARP trial but higher than our results. Another similar study was conducted in 8 medical centres in South America (South American Liver Research Network) and included 127 patients treated with sorafenib over the period 2010-2017 [21]. The median OS was 8.0 months (interquartile range 2 to 17) in line with our results.…”

Section: Discussionsupporting

confidence: 86%

Treatment Patterns and Survival in Patients with Intermediate, Advanced, or Terminal Stage of Hepatocellular Carcinoma in France over the Period 2015-2017: A Real-Life Study

et al. 2023

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Background. The prognosis of patients with hepatocellular carcinoma (HCC) not eligible to curative treatment is poor. Little information is available on treatment modalities and outcomes of these patients in everyday practice. The aim of this analysis was to describe the characteristics of patients with a newly diagnosed intermediate, advanced, or terminal (IAT) stage of HCC (ICD-10: C220) between 2015 and 2017, either present at diagnosis of HCC or having occurred after disease progression; treatment patterns, HCC aetiologies, and the associated survival were determined using the nationwide claims database. Methods. Patients with HCC were identified using the ICD-10 code C220. IAT stages, defined according to the terminology used in the Barcelona Clinic Liver Cancer classification, were indirectly identified by the presence of at least one of the following treatments: transarterial chemoembolization (TACE), transarterial radioembolization (TARE), HCC systemic therapy, best supportive care (BSC), or an ICD-10 code of metastatic HCC. Treatment patterns were described with an algorithm based on a ranking of palliative treatments identified. Survival was analysed by using Kaplan-Meier curves. Results. 19,649 eligible patients were identified. Their mean age was 70.5 years (SD: 11.0), and 82.5% were males. For 68.8% of patients, the IAT stage was present at HCC diagnosis. On the whole population, 5,114 patients (26.0%) were treated initially with a TACE or TARE, and 4,681 (23.8%) received a targeted systemic therapy at any moment during follow-up with sorafenib in 99.5% of cases. About 7,628 patients (45.6%) received only BSC. Survival since the diagnosis of the AIT stage of HCC differed according to the type of the first received palliative treatment. Median overall survival was 23.8, 9.6, 7.4, and 1.0 months in patients initially receiving TACE, TARE, systemic therapy, and BSC only, respectively. Conclusion. Over the period 2015-2017, hepatocellular carcinoma was still often diagnosed in France at late-stage disease with a very poor prognosis.

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Section: Discussionsupporting

confidence: 86%

Treatment Patterns and Survival in Patients with Intermediate, Advanced, or Terminal Stage of Hepatocellular Carcinoma in France over the Period 2015-2017: A Real-Life Study

et al. 2023

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“…When the liver is exposed to alcohol, drugs, and pollutants, its progression toward damage initiates hepato steatosis, fibrosis, and cirrhosis. This exposure results in the death of hepatocytes and, as a consequence, the level of various liver enzymes and metabolites are altered, indicating the anomaly (Sheriff et al, 2017; Balderramo et al, 2018; Hu et al, 2018). Hepatocytes may be injured in various circumstances such as a toxic environment, alcohol, virus, fatty acid metabolism, or chronic antibiotics exposure.…”

Section: Detailed Mechanism Of Hepatoprotectionmentioning

confidence: 99%

“…It demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumor growth and metastatic progression of cancer (Adnane et al, 2006). Sorafenib is a well-known antihepatotoxic drug available in market but the product of its metabolism has been seen to be toxic, affecting other parts of the body with long-term exposure resulting in renal and pancreatic failure (Randrup Hansen et al, 2017; Balderramo et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Role of Natural Phenolics in Hepatoprotection: A Mechanistic Review and Analysis of Regulatory Network of Associated Genes

et al. 2019

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The liver is not only involved in metabolism and detoxification, but also participate in innate immune function and thus exposed to frequent target Thus, they are the frequent target of physical injury. Interestingly, liver has the unique ability to regenerate and completely recoup from most acute, non-iterative situation. However, multiple conditions, including viral hepatitis, non-alcoholic fatty liver disease, long term alcohol abuse and chronic use of medications can cause persistent injury in which regenerative capacity eventually becomes dysfunctional resulting in hepatic scaring and cirrhosis. Despite the recent therapeutic advances and significant development of modern medicine, hepatic diseases remain a health problem worldwide. Thus, the search for the new therapeutic agents to treat liver disease is still in demand. Many synthetic drugs have been demonstrated to be strong radical scavengers, but they are also carcinogenic and cause liver damage. Present day various hepatic problems are encountered with number of synthetic and plant based drugs. Nexavar (sorafenib) is a chemotherapeutic medication used to treat advanced renal cell carcinoma associated with several side effects. There are a few effective varieties of herbal preparation like Liv-52, silymarin and Stronger neomin phages (SNMC) against hepatic complications. Plants are the huge repository of bioactive secondary metabolites viz; phenol, flavonoid, alkaloid etc. In this review we will try to present exclusive study on phenolics with its mode of action mitigating liver associated complications. And also its future prospects as new drug lead.

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“… 3 In these cases, sorafenib, which is a multikinase inhibitor, represents the standard therapy for patients with advanced HCC and in intermediate-stage that are not eligible for locoregional therapies. 3 , 4 In most studies carried out, sorafenib has shown improved survival when compared with placebo. 5 Sorafenib can block tumor cell proliferation by inhibiting the activity of RAF-1, B-RAF and other kinases in the RAS/RAF/MEK/ERK signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

A Combined Antitumor Strategy Mediated by a New Targeted Nanosystem to Hepatocellular Carcinoma

Farinha¹,

Migawa²,

Sarmento‐Ribeiro³

et al. 2021

IJN

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Background: Hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death. Sorafenib, which is the first-line therapy for this disease, is associated with reduced therapeutic efficacy that could potentially be overcome by combination with selumetinib. In this context, the main goal of this work was to develop a new nanosystem, composed of a polymeric core coated by a lipid bilayer containing the targeting ligand GalNAc, to specifically and efficiently co-deliver both drugs into HCC cells, in order to significantly increase their therapeutic efficacy. Methods: The physicochemical characterization of hybrid nanosystems (HNP) and their components was performed by dynamic light scattering, zeta potential, matrix-assisted laser desorption ionization -time of flight mass spectroscopy, and transmission electron microscopy. Cellular binding, uptake and specificity of HNP were evaluated through flow cytometry and confocal microscopy. The therapeutic activity was evaluated namely through: cell viability by the Alamar Blue assay; cell death by flow cytometry using FITC-Annexin V; caspases activity by luminescence; mitochondrial membrane potential by flow cytometry; and molecular target levels by Western blot. Results: The obtained data show that these hybrid nanosystems present high stability and loading capacity of both drugs, and suitable physicochemical properties, namely in terms of size and surface charge. Moreover, the generated formulation allows to circumvent drug resistance and presents high specificity, promoting great cell death levels in HCC cells, but not in non-tumor cells. This potentiation of the antitumor effect of co-loaded drugs was carried out by an increased programmed cell death, being associated with a strong reduction in the mitochondrial membrane potential, a significant increase in the activity of caspases 3/7 and caspase 9, and much greater number of annexin V-positive cells. Conclusion:The developed formulation resulted in a high and synergistic antitumor effect, revealing a translational potential to improve therapeutic approaches against HCC.

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Sorafenib for Treatment of Hepatocellular Carcinoma

Abstract: Pretreatment elevation of platelets and advanced BCLC stage were independently associated with poor survival on sorafenib in a South American cohort.

Cited by 21 publications

References 34 publications

Treatment Patterns and Survival in Patients with Intermediate, Advanced, or Terminal Stage of Hepatocellular Carcinoma in France over the Period 2015-2017: A Real-Life Study

Treatment Patterns and Survival in Patients with Intermediate, Advanced, or Terminal Stage of Hepatocellular Carcinoma in France over the Period 2015-2017: A Real-Life Study

Role of Natural Phenolics in Hepatoprotection: A Mechanistic Review and Analysis of Regulatory Network of Associated Genes

A Combined Antitumor Strategy Mediated by a New Targeted Nanosystem to Hepatocellular Carcinoma

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